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阿尔茨海默病与心血管疾病之间的因果关系:双向孟德尔随机化分析。

Causal relationship between Alzheimer's disease and cardiovascular disease: a bidirectional Mendelian randomization analysis.

机构信息

College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Aging (Albany NY). 2023 Sep 2;15(17):9022-9040. doi: 10.18632/aging.205013.

DOI:10.18632/aging.205013
PMID:37665672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10522384/
Abstract

Observational studies suggest that cardiovascular disease (CVD) increases the risk of developing Alzheimer's disease (AD). However, the causal relationship between the two is not clear. This study applied a two-sample bidirectional Mendelian randomization method to explore the causal relationship between CVD and AD. Genome-wide association study (GWAS) data from 46 datasets of European populations (21,982 cases of AD and 41,944 controls) were utilized to obtain genetic instrumental variables for AD. In addition, genetic instrumental variables for atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), coronary heart disease (CHD), angina pectoris (AP), and ischemic stroke (IS) (including large-artery atherosclerotic stroke [LAS] and cardioembolic stroke [CES]) were selected from GWAS data of European populations ( < 5E-8). The inverse variance weighting method was employed as the major Mendelian randomization analysis method. Genetically predicted AD odds ratios (OR) (1.06) (95% CI: 1.02-1.10, = 0.003) were linked to higher AP analysis. A higher genetically predicted OR for CES (0.9) (95% CI 0.82-0.99, = 0.02) was linked to a decreased AD risk. This Mendelian randomized study identified AD as a risk factor for AP. In addition, CES was related to a reduced incidence of AD. Therefore, these modifiable risk factors are crucial targets for preventing and treating AD.

摘要

观察性研究表明心血管疾病(CVD)会增加患阿尔茨海默病(AD)的风险。然而,两者之间的因果关系尚不清楚。本研究应用两样本双向孟德尔随机化方法探讨 CVD 与 AD 之间的因果关系。使用来自欧洲人群的 46 个数据集的全基因组关联研究(GWAS)数据(21982 例 AD 和 41944 例对照)获得 AD 的遗传工具变量。此外,从欧洲人群的 GWAS 数据中选择了心房颤动(AF)、心力衰竭(HF)、心肌梗死(MI)、冠心病(CHD)、心绞痛(AP)和缺血性中风(IS)(包括大动脉粥样硬化性中风[LAS]和心源性栓塞性中风[CES])的遗传工具变量( < 5E-8)。反方差加权法是主要的孟德尔随机化分析方法。与较高的 AP 分析相关的是遗传预测 AD 的比值比(OR)(1.06)(95%CI:1.02-1.10, = 0.003)。与 CES 相关的遗传预测 OR 较低(0.9)(95%CI 0.82-0.99, = 0.02)与 AD 风险降低相关。这项孟德尔随机研究发现 AD 是 AP 的一个危险因素。此外,CES 与 AD 发病率降低有关。因此,这些可改变的风险因素是预防和治疗 AD 的关键目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/89040c984c87/aging-15-205013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/b88857989c80/aging-15-205013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/06c741893296/aging-15-205013-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/eeba3ea31852/aging-15-205013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/24e25ef31993/aging-15-205013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/89040c984c87/aging-15-205013-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/b88857989c80/aging-15-205013-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/06c741893296/aging-15-205013-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/eeba3ea31852/aging-15-205013-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/24e25ef31993/aging-15-205013-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7552/10522384/89040c984c87/aging-15-205013-g005.jpg

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